In Vivo Purging of Circulating CD34+ Progenitor Cells in Low-Grade Lymphoma With Rituximab and High-Dose Chemotherapy

In Vivo Purging of Circulating CD34+ Progenitor Cells in Low-Grade Lymphoma With Rituximab and High-Dose Chemotherapy

With the aim to overcome the limitations of ex vivo bone marrow
purging, we have assessed the ability of the anti-CD20 monoclonal
antibody rituximab (Rituxan), given in combination with chemotherapy,
to eradicate polymerase chain reaction (PCR)detectable disease,
and to enable the harvesting of large amounts of uncontaminated
peripheral blood progenitor cells in patients with low-grade lymphoma
(in vivo purging). From April 1997 to July 1998, 20 consecutive
patients entered the study. Eligibility included age £
60 years, a diagnosis of untreated mantle cell lymphoma or of
refractory/early relapsed follicular lymphoma, CD20 expression by
tumor cells, histologic bone marrow infiltration, and availability of
a molecular marker for minimal residual disease detection.

Peripheral blood progenitor cells were obtained by leukapheresis when
the CD34+ cell count reached ³
50/µL. The intention was to collect, after cyclophosphamide, a
PCR-negative leukapheresis product containing a minimum of 11 × 106/kg
CD34+ cells. In the case of PCR-positive products, additional
leukaphereses were performed after cytarabine. If the product was
still PCR-positive, ex vivo immunologic purging with an anti-CD19
monoclonal antibody was performed, using a Miltenyi SuperMACS device.
The results are summarized as follows:

CONCLUSION: We showed that rituximab, in combination with one or two
courses of an effective high-dose antilymphoma therapy (in fact, this
strategy was able to produce clinical remissions in 9 out of 10 such
cases), allowed the harvesting of large amounts of tumor-free
progenitor cells in all evaluable patients, including the 4 patients
with mantle cell lymphoma. This in vivo purging strategy compares
very favorably with ex vivo purging in terms of feasibility, costs,
and overall success rate in harvesting an amount of uncontaminated
CD34+ cells (ie, ³ 11× 106/kg)
fully adequate to support more than one cycle of subsequent
myeloablative chemotherapy.